Ricerc@Sapienza

Despite of recent progress in understanding the neurobiology and pathophysiology of Alzheimer¿s disease (AD), no resolutive pharmacological treatments but only a few symptomatic drugs are currently available to patients. Based on this consideration, much effort is aimed at the development of effective prevention lines: accumulation of epidemiological evidence suggests that there is a positive correlation between diet and AD, suggesting the possibility of take action on these important modifiable risk factors to counteract the progression of the disease.
Ketogenic diet (KD) has high fat content, adequate protein intake, but insufficient amounts of carbohydrates, so that the body is forced to use mainly fats as an energy source. The effect of KD supplementation in AD is quite interesting since this disease is preceded by decades of glucose hypometabolism, and earlier dietary intervention might have greater therapeutic effect.
Aims of the present project are:
1) to confirm in in vitro models the anti-inflammatory activity of blueberry polyphenols extracts, studying the activity in relation to the cellular and molecular pathogenic mechanisms underlying the low-grade chronic inflammatory status associated with AD
2) to ascertain the anti-inflammatory activity exerted by ketone bodies or blueberry polyphenolic extracts on microglia stimulated by LPS or Abeta peptide. We will analyze the polarization of the cells towards a pro- or anti-inflammatory phenotype, the synthesis and the release of several cytokines, the cytoskeleton rearrangement influencing migration of the cells
3) in a translational perspective, the in vivo expression of the blueberry polyphenol extract anti-inflammatory activity will be evaluated, through a pilot study, conducted in a sample of subjects suffering from obesity associated with metabolic syndrome, analyzing the effect of fresh blueberry intake in relation to the pro-inflammatory stimulus produced by taking a meal with a known composition